In the long term, diabetes profoundly affects multiple organs, such as the kidney, heart, brain, liver, and eyes. The gradual loss of function in these vital organs contributes to mortality. Nonetheless, the effects of diabetes on the lung tissue are not well understood. Clinical and experimental data from our studies revealed that diabetes induces inflammatory and fibrotic changes in the lung. These changes were mediated by TGF-β-activated epithelial-to-mesenchymal transition (EMT) signaling pathways. Our studies also found that glucose restriction promoted mesenchymal-to-epithelial transition (MET) and substantially reversed inflammatory and fibrotic changes, suggesting that diabetes-induced EMT was mediated in part by the effects of hyperglycemia. Additionally, the persistent exposure of diabetic cells to high glucose concentrations (25 mM) promoted the upregulation of caveolin-1, N-cadherin, SIRT3, SIRT7 and lactate levels, suggesting that long-term diabetes may promote cell proliferation. Taken together, our results demonstrate for the first time that diabetes induces fibrotic changes in the lung via TGF-β1-activated EMT pathways and that elevated SMAD7 partially protects the lung during the initial stages of diabetes. These findings have implications for the management of patients with diabetes.

Cyclin-dependent kinases (cdks) are central catalytic units of cell division cycle. Among the cdk family members, cdk1 has critical roles in multiple phases of the cell cycle. Aberrant expression or hyper-actions of cdk1 are tumorigenic and yet the complex oncogenic network that regulates its turnover is poorly understood. We found a hitherto unexplored functional connection between skp2 and cdk1 turn over. In vitro knockdown or overexpression of skp2 in cultured cells reduced or induced cdk1 expression indicating skp2 as a positive driver for cdk1. A partial inhibitory role for p27 was identified in this context. Interestingly, concurrent overexpression of skp2 and p27 favored cdk1 upregulation in vitro, which correlated well with similar observations in clinical tumor samples. We found that the transcription factor FOXM1 may play a central role in the skp2-cdk1 loop. Additional molecular involvement in the skp2-cdk1 loop was also explored. In conclusion, our results revealed hitherto unexplored p27 independent molecular mechanisms for skp2 driven tumor progression. Our results support the previous findings that skp2 may be a potential therapeutic target for the management of tumors. J. Cell. Biochem. 118: 797-807, 2017. © 2016 Wiley Periodicals, Inc.

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Introduction: Testis is affected by both neoplastic and non-neoplastic conditions which can present in all the age groups. Tumor-like proliferations from paratestis often mimic malignancy which results in unnecessary radical orchidectomy. Hence, one has to depend on histopathologic examination for definitive diagnosis. The testicular tumors although relatively rare, are of great interest and importance because of their varied histological appearances. They account for less than 1% of all malignancies in male. Non-neoplastic lesions or tumor-like proliferations from paratestis often mimic malignancy arising from the scrotal sac which results in unnecessary radical orchidectomy. Hydrocele is often associated with trauma and inguinal hernia, rarely it can be secondary to testicular cancer. Whereas pyocele is most often associated with epididymo-orchitis and less often from contiguous spread of bacterial peritonitis. Hence detailed history and pathological examination are required to know the underlying cause. Objective: To know the morphological spectrum of testicular and paratesticular lesions, their incidence in different age groups, laterality, incidence of benign versus malignant lesions and to study their gross, microscopic features. Methodology: This is a 2 years retrospective study from June 2017 to May 2019 at department of pathology, ESIC Medical college, Kalaburagi. Gross specimens, slides and blocks were retrieved and reviewed. Results: Total 49 cases were studied of which 26 were testicular lesions and 23 paratesticular lesions. Non neoplastic testicular lesions were more common than neoplastic lesions (96.1% Vs 3.8%) with majority in the fifth and sixth decade. Right testis was more commonly involved (59.09%) than left testis (31.8%) and bilateral involvement was seen in 9% cases. Atrophic testis was most common testicular lesion whereas Pyocele was most common paratesticular pathology. Conclusion: Testis and paratestis can develop both non neoplastic and neoplastic lesions. Gross morphology can give important clues for pathological diagnosis. However there is a crucial role of microscopic examination for definitive diagnosis of these lesions.

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